Disruptions in Effective Connectivity within and between Default Mode Network and Anterior Forebrain Mesocircuit in Prolonged Disorders of Consciousness

Recent research indicates prolonged disorders of consciousness (PDOC) result from structural and functional impairments to key cortical and subcortical networks, including the default mode network (DMN) and the anterior forebrain mesocircuit (AFM). However, the specific mechanisms which underpin such impairments remain unknown. It is known that disruptions in the striatal-pallidal pathway can result in the over inhibition of the thalamus and lack of excitation to the cortex that characterizes PDOC. Here, we used spectral dynamic causal modelling and parametric empirical Bayes on rs-fMRI data to assess whether DMN changes in PDOC are caused by disruptions in the AFM. PDOC patients displayed overall reduced coupling within the AFM, and specifically, decreased self-inhibition of the striatum, paired with reduced coupling from striatum to thalamus. This led to loss of inhibition from AFM to DMN, mostly driven by posterior areas including the precuneus and inferior parietal cortex. In turn, the DMN showed disruptions in self-inhibition of the precuneus and medial prefrontal cortex. Our results provide support for the anterior mesocircuit model at the subcortical level but highlight an inhibitory role for the AFM over the DMN, which is disrupted in PDOC.

A Novel Pharmacogenetic Model for Highly Efficient Ablation of Oligodendrocyte Progenitor Cells in the Adult Mouse CNS

Approaches to investigate adult oligodendrocyte progenitor cells (OPCs) by targeted cell ablation in the rodent central nervous system have been limited by methodological challenges resulting in only partial and transient OPC depletion. We have developed a novel pharmacogenetic model of conditional OPC ablation, resulting in the elimination of 99.7% of all OPCs throughout the brain. By combining recombinase-based transgenic and viral strategies for targeting of OPCs and ventricular-subventricular zone (V-SVZ)-derived neural precursor cells (NPCs), we found that new PDGFRα-expressing cells born in the V-SVZ repopulated the OPC-deficient brain starting 12 days after OPC ablation. Our data reveal that OPC depletion induces V-SVZ-derived NPCs to generate vast numbers of PDGFRα+/NG2+ cells with the capacity to migrate and proliferate extensively throughout the dorsal anterior forebrain. Further application of this novel approach to ablate OPCs will advance knowledge of the function of both OPCs and oligodendrogenic NPCs in health and disease.

Disruptions in effective connectivity within and between default mode network and anterior forebrain mesocircuit in prolonged disorders of consciousness

Recent research indicates prolonged disorders of consciousness (PDOC) result from structural and functional impairments to key cortical and subcortical networks including the default mode network (DMN) and the anterior forebrain mesocircuit (AFM). However, the specific mechanisms which underpin such impairments remain unknown. It is known that disruptions in the striatal-pallidal pathway can result in the over inhibition of the thalamus and lack of excitation to the cortex that characterises PDOC. Here, we used spectral dynamic causal modelling and parametric empirical Bayes on rs-fMRI data to assess whether DMN changes in PDOC are caused by disruptions in the AFM. PDOC patients displayed overall reduced coupling within the AFM, and specifically, decreased self-inhibition of the striatum paired with reduced coupling from striatum to thalamus. This led to loss of inhibition from AFM to DMN, mostly driven by posterior areas including the precuneus and inferior parietal cortex. In turn, the DMN showed disruptions in self-inhibition of the precuneus and medial prefrontal cortex. Our results provide support for the anterior mesocircuit model at the subcortical level but highlight an inhibitory role for the AFM over the DMN, which is disrupted in PDOC.

A Relationship between the Characteristics of the Oval Nucleus of the Mesopallium and Parrot Vocal Response to Playback

Correlations between differences in animal behavior and brain structures have been used to infer function of those structures. Brain region size has especially been suggested to be important for an animal’s behavioral capability, controlled by specific brain regions. The oval nucleus of the mesopallium (MO) is part of the anterior forebrain vocal learning pathway in the parrot brain. Here, we compare brain volume and total number of neurons in MO of three parrot species (the peach-fronted conure, <i>Eupsittula aurea</i>, the peach-faced lovebird, <i>Agapornis roseicollis</i>, and the budgerigar, <i>Melopsittacus undulatus</i>), relating the total neuron numbers with the vocal response to playbacks of each species. We find that individuals with the highest number of neurons in MO had the shortest vocal latency. The peach-fronted conures showed the shortest vocal latency and largest number of MO neurons, the peach-faced lovebird had intermediary levels of both, and the budgerigar had the longest latency and least number of neurons. These findings indicate the MO nucleus as one candidate region that may be part of what controls the vocal capacity of parrots.

The Adjustment of Anterior Forebrain Pathway (AFP) to Birdsong Is Phased during Song Learning and Maintenance

Anterior forebrain pathway (AFP), a basal ganglia-dorsal forebrain circuit, significantly impacts birdsong, specifically in juvenile or deaf birds. Despite many physiological experiments supporting AFP’s role in song production, the mechanism underlying it remains poorly understood. Using a computational model of the anterior forebrain pathway and song premotor pathway, we examined the dynamic process and exact role of AFP during song learning and distorted auditory feedback (DAF). Our simulation suggests that AFP can adjust the premotor pathway structure and syllables based on its delayed input to the robust nucleus of the archistriatum (RA). It is also indicated that the adjustment to the synaptic conductance in the song premotor pathway has two phases: normal phases where the adjustment decreases with an increasing number of trials and abnormal phases where the adjustment remains stable or even increases. These two phases alternate and impel a specific effect on birdsong based on AFP’s specific structures, which may be associated with auditory feedback. Furthermore, our model captured some characteristics shown in birdsong experiments, such as similarities in pitch, intensity, and duration to real birds and the highly abnormal features of syllables during DAF.